Basic bisarylsulfides



United States Patent 3,332,960 BASIC BISARYLSULFIDES Lincoln HarveyWerner, Summit, N.J., assignor to Ciba Corporation, New York, N.Y., acorporation of Delaware No Drawing. Filed Apr. 27, 1964, Ser. No.363,001

a Claims. (Cl. 260-309.6)

The present invention concerns bis-aryl-sulfides. More particularly, itrelates to compounds of the formula Ar --XAr in which X is thio of theformula --S-, sulfinyl of the formula -SO-, or sulfonyl of the formulaSO and each of the groups Ar and Ar is monocyclic carbocyclic arylsubstituted by R-methoxy, in which R is a 1,3-diaza-2-cycloalken-2-ylgroup of five to seven ring members, or salts of such compounds, as wellas process for the preparation of such compounds. The above compoundsare more especially represented by the formula Ar-XAr, in which X hasthe abovegiven meaning, and each of the groups Ar is monocycliccarbocyclic aryl substituted by R-methoxy, in which R has thepreviously-given meaning.

The monocyclic carbocyclic aryl groups Ar, and Ar have preferably oneR-methoxy group, but may have more than one; usually an R-methoxy groupsubstitutes the 4-position of the monocyclic carbocyclic aryl group.

The group R in an R-methoxy substituent, which is a2-l,3-diaza-2-cycloalken-2-yl radical of five to seven ring members, ismore particularly a 2-imidazolin-2-yl radical, but may also be a1,4,5,6-tetrahydro-pyrimidin-2-yl or a l,3-diaza-2-cyclohepten-2-ylradical, The carbon atoms of the 1,3-aza-2-cycloalken-2-yl radicalavailable for substitution, as well as one of its aza-nitrogen ringmembers, may be substituted, for example, by lower alkyl, e.g. methyl,ethyl, n-propyl, isopropyl, n-butyl, tertiary butyl and the like.

The 1,3-diaza-2-cycloalken-2-yl radical may be represented by thepartial formula:

in which R, is hydrogen or lower alkyl, and A is lower alkyleneseparating the two nitrogen atoms by two to four carbon atoms. Thelatter may be represented above all by 1,2-ethy1ene, but may also be1-methyl-1,2-ethylene, 1,1dimethyl-1,2-ethylene,l,2-dimethyl-l,2-ethylene, 1,3- propylene, 1-methyl-1,3-propylene,2,2-dimethyl-1,3-propylene, 1,3-dimethyl-1,3-propylene,1-ethyl-1,3-propylene, 1,4-butylene, 1-methyl-l,4-butylene and the like.

The two monocyclic carbocyclic aryl groups substituted by R-methoxy maybe otherwise unsubstituted or may contain one or more than oneadditional substituent, which may be attached to any position availablefor additional substituents. The latter are, for example, lower alkyl,e.g. methyl, ethyl, n-propyl, isopropyl, 1,1-dimethyl-propyl, n-butyl,isobutyl, secondary butyl, tertiary butyl and the like, or substitutedlower alkyl, such as halogenomethyl, e.g. trifluoromethyl and the like,or N,Ndisubstituted amino-methyl, such as N,N-di-loweralkyl-aminomethyl, e.g. N,N-dimethylaminomethyl, N,N-diethylaminomethyland the like, N,N-alkylene-imino-methyl, in which alkylene has from fourto seven chain carbon atoms, e.g. l-pyrrolidinomethyl,l-piperidinomethyl and the like, 4-lower alkyl-l-piperazino-methyl, e.g.4-methyll-piperazinomethyl and the like, 4-morpholinomethyl, or anyother analogous substituted lower alkyl group, such as phenyl-loweralkyl, e.g. benzyl and the like, cycloalkyl having from three to eight,preferably from five to six,

"ice

ring carbon atoms, e.g. cyclopentyl, cyclohexyl and the like, halogeno,e.g. fluoro, chloro, bromo and the like, or any other suitablesubstituent, such as R-methoxy having the above-given meaning.

Salts of the compounds of this invention are acid addition salts, suchas the pharmaceutically acceptable acid addition salts with inorganicacids, e.g. hydrochloric, hydrobromic, sulfuric, phosphoric acids andthe like, or with organic acids, such as organic carboxylic acids, e.g.formic, acetic, propionic, glycolic, malonic, succinic, maleic,hydroxy-maleic, fumaric, malic, tartaric, citric, benzoic, cinnamic,salicylic, 4-aminosalicylic, 2-phenoxybenzoic, 2-acetoxybenzoic acid andthe like, or organic sulfonic acids, e.g. methane sulfonic, ethanesulfonic, 2 -hydroxyethane sulfonic, ethane 1,2-disulfonic, benzenesulfonic, p-toluene sulfonic, naphthalene 2-sulfonic acid and the like.Other acid addition salts are used as intermediates, for example, in thepurification of the free compounds or in the preparation of other, forexample, pharmaceutically acceptable acid addition salts, as well as foridentification and characterization purposes. Acid addition salts, whichare primarily used for the latter are, for example, those with certaininorganic acids, e.g. perchloric acid and the like, with acidic organicnitro compounds, e.g. picric, picrolonic, fiavianic acid and the like,or with metal complex acids, e.g. phosphotungstic, phosphomolybdic,chloroplatinic, Reinecke acid and the like.

.T he new compounds of this invention have anti-inflammatory propertiesas demonstrated in the granuloma pouch test (Selye, Proc. Soc. Exp.Biol. & Med., vol. 82, p. 328 (1953), as modified by Robert et al., ActaEndrocrinologica, vol. 25, p. (1957)), the cotton pellet implant test(Meier et al., Experientia, vol. 6, p. 469 (1950)), or the pleuralcavity inflammation test (Holtcamp, Fed. Proc., vol. 17, p. 379 (1958)).They are, therefore, useful as anti-inflammatory agents in place ofcertain corticoid steroids, e.g. cortisone, hydrocortisone and the like,in the treatment of tissue inflammations, such as arthriticinflammations and the like.

Compounds of this invention also have anti-parasite, particularly,taeniacidal (anti-tapeworm) properties, and are, therefore, useful astaeniacides in the treatment of tapeworminfections, caused, for example,by Hymenolepas nana, Dypilidium canium, Taenia pr'siformis and the like.

Particularly useful are the compounds of the formula:

in which X has the previously-given meaning, but is more especially thioof the formula S, A stands for alkylene having from two to three carbonatoms and separating the two nitrogen atoms by from two to three carbonatoms, R is primarily hydrogen, as well as lower alkyl, and each of thegroups R and R is hydrogen, lower alkyl or halogeno, or acid additionsalts, particularly pharmaceutically acceptable, non-toxic acid additionsalts thereof.

The compounds of this invention are useful in the form of compositionsfor enteral, e.g. oral, parenteral o1 topical use, which compriseessentially a pharmacologically effective amount of one of the newcompounds 01 this invention in admixture with a pharmaceuticallyacceptable, organic or inorganic, solid or liquid carrier the latterusually represents the major portion of the com position. The latter arein solid form, for example, it the form of capsules, tablets, drageesand the like, or ir liquid form, for example, in the form of solutions,suspensions, and the like, or in emulsified form, for example, in theform of salves, creams, lotions and the like. For making up thecompositions, there are employed substances used in the art ofmanufacturing pharmaceutical :ompositions, such as water, gelatin,saccharides, e.g. ,actose, glucose and the like, starches, e.g. wheatstarch, :orn starch and the like, stearic acid or salts thereof, e.g.nagnesium stearate, calcium stearate and the like, talc, legetable oils,benzyl alcohol, stearyl alcohol, cetyl alcorol, petrolatum, gums,acacia, tragacanth, sodium lauryl :ulfate, propylene glycol,polyalkylene glycols, or any )ther carrier materials suitable for makingup the com- )ositions. The quantity and the nature of the carrieringredients can vary widely and depend, inter alia, upon he desiredphysical appearance or size of the composiion, method of manufacture andthe like. Encapsulation nay be effected by using, if desired, the sameexcipients is those for tablets. If necessary, the compositions may:ontain auxiliary substances, such as preserving, stabilizng, wetting,emulsifying, coloring, flavoring agents and he like, salts for varyingthe osmotic pressure, buffers, =tc. The compositions, which are preparedaccording to :nown methods, usually by forming mixtures of thepharnacologically active ingredient and the carrier materials, fnecessary, granulates for subsequent compression, may llSO contain, incombination, other useful substances. \ny compatible color, approved andcertified under the urovisions of the Federal Food, Drug and CosmeticLaw may be used for aesthetic purposes or as a means of idenification.

The compounds of the present invention are prepared .ccording to knownmethods, for example, by converting n a compound of the formula Ar -XArin which i has the previously given meaning, and each of the roups Arand Ar is monocyclic carbocyclic aryl submitted by R capable of beingconverted into R-methoxy, r1 which R has the previously-given meaning,or a salt hereof, the group R into R-methoxy, in which R has repreviously-given meaning, and, if desired, converting 1 a resultingcompound the group X into another group epresenting X, and/or, ifdesired, converting a resulting alt into the free compound or intoanother salt, and/or, desired, replacing in a resulting compound havinga ydrogen substituting one of the aza-nitrogen atoms of rel,3-diaza-2-cycloalken-2-yl radical by lower alkyl, nd/or, if desired,converting a free compound into a alt thereof.

The above starting material is more especially repreented by the formulaArXAr, in which X has the reviously-given meaning, and each of thegroups Ar :presents a monocyclic carbocyclic aryl radical substilted byR capable of being converted into R-methoxy, l which R has thepreviously-given meaning. Groups capable of being converted intoR-methoxy, are above ll hydroxyl, as well as reactive functionallyconverted irboxy-methoxy groups.

In a starting material, in which R is hydroxyl, such roup is convertedinto R-methoxy, for example, by re- :ting it or a salt thereof with areactive ester of an R- ethanol, in which R has the previously-givenmeaning, a. is a l,3-diaza-2-cycloalken-2-yl radical, or a salt there-E.

The salt of a starting material, in which R is hydroxyl,

primarily a metal salt, particularly an alkali metal, e.g. )dium,potassium and the like, salt, as well as an alkaline rrth metal saltthereof, or any other suitable s-alt. Such .lt is prepared according toknown methods, for example, 1 reacting the free starting material with ametal, par- :ularly an alkali metal, or, more especially, with a etal,especially an alkali metal, hydride, amide or lower koxide, e.g.methoxide, ethoxide, tertiary butoxide and e like, in the presence of anappropriate diluent.

The reactive esterified R-rnethanol used as the reagent the abovereaction is above all the ester of such alcohol ith a strong inorganicacid, particularly a hydrohalic acid, e.g. hydrochloric acid,hydrobromic acid or hydriodic acid; other suitable esters are those withsulfuric acid, as well as with strong organic acids, particularly strongorganic sulfonic acids, such as lower alkane sulfonic acids ormonocyclic carbocyclic aryl sulfonic acids, i.e. methane sulfonic,ethane sulfonic, Z-hydroxyethane sulfonic, p-toluene sulfonic acid andthe like. Preferred reactive esters of R-methanol are the R-methylhalides, e.g. chloride and the like. Salts of a reactive ester of anR-methanol are addition salts with acids, such as those mentionedbefore, particularly the hydrohalic acids.

The reaction of the starting material, in which R is hydroxyl, moreparticularly of a salt, especially an alkali metal salt, thereof, withthe reactive ester of an R-methanol or a salt thereof is carried out inthe absence or in the presence of a diluent; the selection of the latterdepends on the properties of the reagents and/or the salt formingreagent. Thus, suitable solvents are, for example, lower alkanols, e.g.methanol, ethanol and the like, ethers, e.g. diethyl ether, p-dioxane,tetrahydrofuran and. the like, hydrocarbons, e.g. hexane, cyclohexane,benzene, toluene and the like, N,N-disubstituted amides, e.g.N,N-dimethylformamide and the like, or any other solvent or solventmixture. The formation of the salt may also be carried out in situ;thus, the starting materials, in which R is hydroxyl, may be mixed withthe reactive esterified R-methan-ol or a salt thereof, and thesaltforming reagent, which may also be, for example, an alkali metalcarbonate, an alkaline earth metal carbonate and the like, may then beadded to the mixture. If necessary, the reaction is carried out whilecooling or at an elevated temperature, in a closed vessel and/or in theatmosphere of an inert gas, e.g. nitrogen.

The starting material used in the above procedure is knOWn and preparedaccording to known methods. Thus, the bis-(monocyclic carbocyclicaryl)-sulfides are obtained, for example, by reacting a phenol compound,such as a compound of the formula ArI-I, in which Ar is a monocycliccarbocyclic aryl radical substituted by R representing hydroxyl, withsulfur dichloride in the presence of carbon disulfide. In a resultingbis-(monocyclic carbocyclic aryl)-sulfide, the thio group may beconverted into a sulfinyl group or a sulfonyl group according to knownoxidation methods; the oxidation of the thi-o group into a sulfinylgroup is carried out by oxidation with hydrogen peroxide in the presenceof glacial acetic acid while cooling, with an organic per-acid, e.g.peracetic, perbenzoic, monoperphthalic acid and the like at lowtemperatures, with chromic acid in the presence of acetic acid and undermild conditions, with nitric acid or any other suitable reagent, whereasits conversion int-o the sulfonyl group is performed by treatment withhydrogen peroxide or organic peracids at room temperature or preferablyat elevated temperatures, with potassium permanganate in the presence ofan acid, e.g. acetic, dilute sulfuric acid and the like. Bis-(monocycliccarbocyclic aryl)-sulfoxides may also be obtained by reacting a phenolcompound, such as a compound of the formula ArH, in which Ar is amonocyclic carbocyclic aryl radical substituted by hydroxyl, withaluminum chloride in the presence of carbon disulfide or thionylchloride, whereas a bis-(monocyclic carbocyclic aryl)- sulfone may beobtained by reacting the phenol compound with oleum, i.e. concentratedsulfuric acid containing sulfur tr'ioxide. A resulting bis- (monocycliccarbocyclic aryl)-sulfoxide may be converted into the correspondingsulfide compound by reduction, for example, with zinc and acetic acid orany other suitable reduction procedure.

As noted above, the group R capable of being converted into R-methoxy isalso a reactive functionally converted carboxy-methoxy group. Thereactive functionally converted carboxyl portion of such group isprimarily a cyano group, as well as an imido-ether, an imido-thioether,an imido-halide, an amidino, an amido, a thioamido, and ester, or anacid halide grouping. These groups are represented by the formula:

in which halogeno stands primarly for chloro, as well as bromo and thelike, and R has the above-given meaning, i.e. stands for hydrogen orlower alkyl.

The conversion of a reactive functionally converted carboxyl group intothe desired 1,3-diaza-2-cycloalken-2-yl radical is carried out accordingto known methods. For example, the starting material is reacted with alower alkylene diamine, in which the two amino groups are separated bytwo to four carbon atoms, or with a compound capable of being convertedinto such lower alkylene diamine by treatment with ammonia, or with areactive N- substituted derivative of such lower alkylene diamine. Thedesired ring formation is carried out directly or in stages, ifnecessary, in the presence of a suitable reagent; furthermore, theprocess may be performed in such manner that a functional acidderivative is formed in the course of the reaction.

For example, whenever the preferred starting material, in which R iscyanomethoxy, is reacted directly with the lower alkylene diamine orwith a derivative thereof,

it is of advantage to perform the reaction in the presence of hydrogensulfide, carbon disulfide and the like; in such reaction, the loweralkylene diamine may be used in the form of a salt thereof.

Compounds capable of being converted into a lower alkylene diamine bythe reaction with ammonia, are, for example, the correspondinghydroxy-loweralkyl-amines, or especially the esters thereof, as well aslower alkylene halides. Using these starting materials, the reaction iscarried out in the presence of ammonia or an agent yielding ammonia.

Reactive N-substituted derivatives of the lower alkylene diamines usedas reagents in the above process are ureas, such as, for example,ethylene urea, propylene urea and the like.

To carry out the procedure in stages, the starting material is reactedwith the lower alkylene diamine to form the N-aeyl compound, which isthen ring-closed by elimination of water, for example, by using adehydrating agent,

such as calcium oxide and the like, or by desulfurization, for example,with a heavy metal oxide and the like.

The above reaction is carried out according to known methods; conditionsdepend largely on the choice of the starting material and the reagent.Thus, the reaction may be carried out in the absence or presence of adiluent, catalyst and/ or condensing agent, if necessary, while coolingor at an elevated temperature, under increased pressure, and/or in theatmosphere of an inert gas, such as nitrogen. By-products, formed duringthe reaction, such as water, may be removed, for example, by azeotropicdistillation. Furthermore, one of the reactants may be used in excess ofthe other.

The starting materials used in the above procedure are preparedaccording to known methods. For example, the salt of a compound of theformula Ar X-Ar in which X has the previously-given meaning, and each ofthe monocyclic carbocyclic aryl groups Ar and Ar is substituted byhydroxyl, particularly a compound of the formula ArXAr, in which X hasthe previouslygiven meaning, and each of the groups Ar is monocycliccarbocyclic aryl substituted by hydroxyl, may be treated with a reactiveesterified hydroxy-acetic acid or a reactive functionally converted acidderivative thereof. This reaction is carried out in a manner analogousto the one previously described, involving treatment of a startingmaterial of the formula Rr XAr in which X has the previously-givenmeaning, and each of the monocyclic carbocyclic aryl groups issubstituted by hydroxyl, or a salt thereof, with a reactive ester of anR-methanol or a salt thereof. In any resulting compound a free carboxylgroup or a reactive functionally converted carboxyl group may beconverted into the desired reactive functionally converted carboxylgroup according to methods known per se. Furthermore, in a resultingstarting material, a group X may be converted into another grouprepresenting X according to known methods, for example, those previouslydescribed.

In a resulting compound, in which one of the nitrogen atoms of the1,3-diazo-2-cycloalken-2-yl radical representing R carries a hydrogen,such hydrogen may be replaced by lower alkyl according to known methods.For example, a resulting compound of the formula in which X has thepreviously-given meaning, and in at least one of the twoR-methoxysubstituted monocyclic carbocyclic aryl groups the group R isan N-unsubstituted 1,3-diaza-2-cycloalken-2-yl radical, or a saltthereof, such as an alkali metal salt thereof, may be reacted with areactive ester of a lower alkanol, for example, a lower alkyl halide,e.g. methyl, ethyl or isopropyl chloride, bromide, or iodide and thelike, or a di-lower alkyl sulfate, e.g. dimethyl sulfate, diethylsulfate and the like, to yield the corresponding compound of the formulaAr X-Ar in which X has the previously-given meaning, and at least one ofthe monoeyclic carbocyclic aryl groups Ar and Ar is substituted with anN-lower alkylated (1,3-diaza- 2-cycloalken-2-yl -methoxy group.

In a resulting compound of the formula Ar XAr in which Ar Ar and X havethe previously-given meaning, a group X may be converted into anothergroup representing X. This conversion is carried out according to knownmethods, such as those previously described; it the oxidation of a thiogroup into a sulfinyl or sulfonyI group those oxidation reagents arepreferred, which dc not favor the formation of oxidative degradationprod ucts.

A resulting acid addition salt may be converted intc the free compound,for example, by treatment with at alkaline reagent, such as a metalhydroxide, e.g. sodiun hydroxide, potassium hydroxide, calcium hydroxideant the like, a metal carbonate, e.g. sodium, potassium or cal ciumcarbonate or hydrogen carbonate or hydrogen car bonate and the like,ammonia or any other alkaline re agent, as well as a suitable hydroxylion exchange prep aration, etc.

A resulting acid addition salt may be converted directl into anotheracid addition salt, for example, by treatmen with an anion exchangepreparation. Furthermore, conver sion of one acid addition salt intoanother may also b achieved, for example, by reacting an inorganic acidad dition salt with a suitable metal, e.g. sodium, barium silver and thelike, salt of an acid, in a diluent, in which resulting inorganic saltis insoluble and is thus remove from the reaction medium.

A free compound may be converted into an acid addi tion salt by reactingit or a solution thereof in a suitabl solvent or solvent mixture with anacid, such as one o those described before, or a solution thereof, orwith suitable anion exchange preparation, and isolating 'the de siredsalt. A salt may be obtained in the form of a hydrat or may containsolvent of crystallization.

The invention also comprises any modification of th process wherein acompound formed as an intermediat at any stage of the process, is usedas starting materiz and the remaining step(s) of the process is(are)carrie out, or the process is discontinued at any stage, or i Example 1To a solution of 10.8 g. of bis-(4-hydroxy-2-methyl-5- srtiarybutyl-phenyl)-sulfide in 30 ml. of N,N-dimethylarmamide and 50 ml. oftoluene is added 2.7 g. of a 53 ercent suspension of sodium hydride inmineral oil while tirring and maintaining at atmosphere of nitrogen.After :irring for ten minutes, a solution of 8.5 g. of 2-chloro-1ethyl-2-imidazoline in 110 ml. of toluene is added, and 1e reactionmixture is heated to 50 and maintained at rat temperature for eighthours. After standing overnight, 1e solution is filtered, and the solidmaterial is washed 'ith benzene and N,N-dimethylformamide, then slurriedfiltrate is acidified with a solution of hydrogen chloride in ethylacetate, and the resulting precipitate is filtered off. After washingwith isopropanol and two recrystallizations from a mixture of ethanoland ethyl acetate, this second crop of thebis-[4-(Z-imidazolin-Z-yl-methyl)-oxy- Z-methyI-S-tertiarybutyl-phenyl]-sulfide dihydrochloride, M.P. 285 (yield: 3.5 g.), iscombined with the first crop and is recrystallized from a mixture ofethanol and ethyl acetate; the resulting product melts at 288.

The bis- [4- Z-imidazolin-Z-yl-rnethyl) -ox-y-2-methyl-5- tertiarybutyl-phenyH-sulfide picrate is prepared by reacting bis-[4-(Z-irnid-azolin-Z-yl-methyl) -oxy-2-methyl-5-tertiarybutyl-phenyH-sulfide with picric acid in an appropriate solvent.

Upon reacting bis- [4-(2-imidazolin-2-yl-methyl) -oxy-2-methyl-S-tertiary butyl-phenyl]-sulfide with an excess of methyl iodide,the bis-[4-(l-methy1-2-imidazolin-2-ylmethyl)-oxy-2-methyl-5-tertiarybutyl-phenyH-sulfide dihydriodide is obtained.

Example 2 Other compounds of this invention, which are preparedaccording to the above described and illustrated procedure by selectingthe appropriate starting materials, are,

'ith water and recrystallized from ethyl acetate to yield 25 forexample,

Starting Material Reagent Product .s-(4-hydr0xy-pl1eny1)-sulfides-(4-hydroxy-phenyl)-sulfide .s-(4-hydroxy-2methy1-5 tertiarybutylphenyD-sulfide.

s-(igzgclohexyl-4-hydroxy-s-methyl-phenyl)- su e.s-(2,6-dibenzyl-4-hydroxy-phenyl)-sulfides-(2,6-di-isopropyl-4-hydroxy-phenyl)- sulfide.s-(3,5'dichl0ro-4-hydtoxy-phenyl)-sulfides-(2,6-dichloro-t-hydroxy-phenyl)sulfides-(2-ethy1-4-hydr0xy-phenyl)-sulfides-(2-N,N-diethyl-arninomethyl-3,6-dimethyll-hydroxy-phenyD-sulfide.

s-(3-br0m0-2-chloro-4-hydroxy-phenyl)- in de. plus NaH.s-(4-hydroxy-phenyl)-sulfoxide s(4-hydr0xy-2-methyl-5-tertiary butyl-)henyD-sulfoxide. s-(4-hydroxy-phenyl)-suliones-(4-hydroxy-2-methyl-5-tertiary butyl- )henyD-sulfone.s-(3,4-dihydroxy-phenyl)-sulfide ebis-[4-(2-imidazolin-2-yl-methyl)-oxy-2-methyl-5-tertrybutyl-phenyl1-sulfide of the formula:

2-chloromethyl-2-imidaz0line plus N aH2-chloromethyl-l,4,5,fi-tetra-hydro-pyrimi-dine plgs N aH. o

Z-chloromethyl-Z-imidazoline plus NaH2chloromethyl-4-methyl-2-1midazoline plus 2-c h i3ornothyI-Z-imidazoline plus NaH.

2-ch1oromethyl-1,3-diaza-2-cycloheptene plus NaHethyl-l,4,5,6tetra-hydro-pryimidine 2-0111oroni tihyla-imidazoline plusNaH 2-chlorornethy1-1,4,5,G-tetra-hydro-pyrimidlne2-ehloromethyl-2-imidazoline plus N aH sulfone.Bis-[4-(2-imidazolin-Z-yl-methyl)-oxy-2-1nethyl- 5-tertia-rybutyl-phenyH-sulfone.Bis-[3,4-bis-(Z-imidazolin-Z-yl-methyl)-oxyphenylJ-sulfide.

What is claimed is:

1. A member selected from the group consisting of the compound havingthe formula:

I'M w B1 b Rb in which X is a member selected from the group consistingof thio, sulfinyl and sulfonyl, A is alkylene of from two to threecarbon atoms and separating the two nitrogen atoms by two to threecarbon atoms, R is a member se lected from the group consisting ofhydrogen and lower alkyl, and each of the groups R and R is a memberselected from the group consisting of hydrogen, lower alkyl andhalogeno, and an acid addition salt thereof.

2. A member selected from the group consisting of the compound havingthe formula:

in which A is alkylene of from two to three carbon atoms and separatingthe two nitrogen atoms by two to three carbon atoms, and each of thegroups R and R is a member selected from the group consisting ofhydrogen, lower alkyl and halogeno, and an acid addition salt thereof.

3. Bis [4-(Z-imidazolin-Z-yl-rnethyl)-oxy-2-methyl-5- tertiarybutyl-phenyl1-su1fide.

1O 4. An acid addition salt of bis-[4-(2-irnidaZo1in-2-yimethyl)-oxy-2-met.hyl-5-tertiany butyl-phenyl] -sulfide.

5. Bis [4-(2-imidazo1in-2-y1-methyl)-oXy-2methy1-5- tertiaryb-utyl-phenyl] -su1fide dihydrochloride.

References Cited Cavallini, Chemical Abstracts, vol. 41, column 6989(1947).

Passerini et al.: Gazz. Chim. ItaL, vol. 90, page 1279 10 relied on(1960).

WALTER A. MODANCE, Primary Examiner.

JOHN D. RANDOLPH, Examiner.

15 N. TROUSOF, Assistant Examiner.

1. A MEMBER SELECTED FROM THE GROUP CONSISTING OF THE COMPOUND HAVINGTHE FORMULA: